4-Bromobenzyl bromide → HCID 11361507, compound

Participants

Reaction Steps

To a solution of N-(tert-butoxycarbonyl)proline methyl ester (1.30 g) in THF (20 mL) at −78° C. was added a solution of KHMDS (1.25 g) in THF (20 mL). After 45 minutes, a solution of 4-bromobenzyl bromide (1.59 g) in THF (20 mL) was added at −78° C. The reaction mixture was warmed to room temperature over 3 hours and stirred for an additional 3 hours. The mixture was diluted with EtOAc, washed with water and brine, dried (Na2SO4), filtered and concentrated. Purification by flash column chromatography (silica gel; EtOAc/hexane 1:2) afforded N-(tert-butoxycarbonyl)-2-(4-bromobenzyl)proline methyl ester (0.474 g). MS (m/z) 398 (MH+). (2) To a solution of the compound obtained above (0.474 g) in CH2Cl2 (5 mL) was added TFA (1.5 mL). After 1 hour, the reaction mixture was diluted with CH2Cl2, washed with aqueous NaHCO3 and brine, dried (Na2SO4) and concentrated to give 2-(4-bromobenzyl)proline methyl ester. MS (m/z) 298 (MH+). (3) 3,5-Dichlorophenylisocyanate (0.50 g) was added to a solution of the compound obtained above in THF (10 mL) and DIEA (2.0 mL). After 4 hours stirring at room temperature, the reaction mixture was concentrated. The residue was redissolved in EtOAc, washed with aqueous NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. Purification by chromatography (silica gel: EtOAc/hexane: 1/4, Chromatotron (Harrison Research)) afforded 0.33 g of N-[(3,5-dichlorophenyl)carbamoyl]-2-(4-bromobenzyl)proline methyl ester. MS (m/z) 485 (MH+). mp 170.9° C. (4) The compound obtained above (0.153 g) was dissolved in hot EtOH (10 mL) and cooled to 0° C. To the solution at 0° C. was added NaOEt (0.010 g). After 45 minutes of stirring, the mixture was concentrated. Purification by chromatography (silica gel: 15% EtOAc/hexane, Chromatotron) afforded the titled compound (0.129 g). MS (m/z) 453 (MH+). mp 69.4° C.

Provenance & Evidence